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Biomedical subjects

J Finley

Publications and source records attributed to J Finley.

At least 19 recordsLinked to original sources

Paucity of CFTR current but modest CFTR immunoreactivity in non-diseased human ventricle.

We looked for evidence of expression of the cystic fibrosis transmembrane conductance regulator (CFTR) in non-diseased human ventricle. In rabbit and guinea pig the CFTR current is present in the highest density in subepicardial ventricular myocytes. In the present study, whole-cell patch-clamp was used to determine if a CFTR-like chloride current (I(CFTR,card)) can also be activated in human subepicardial ventricular myocytes. No evidence for I(CFTR,card) was detected in these electrophysiological studies when 10 microM forskolin was applied to 23 different cells from 4 donor hearts. Consistent with our previous results, a swelling-induced chloride current (I(Cl,swell)) could be observed after cell inflation. The enzymatic digestion of human ventricle to release single myocytes may have affected our ability to detect I(CFTR,card). Therefore, we looked for anti-CFTR immunoreactivity in slices of left ventricular free wall. A strong immunoreactivity signal was observed in guinea pig ventricle, a positive control. Background staining levels were seen in dog ventricle, a negative control tissue. Human anti-CFTR immunoreactivity was slightly above background. This low level of anti-CFTR immunoreactivity is consistent both with reports that CFTR mRNA is detectable in human ventricle and our inability to detect a significant I(CFTR,card) current density.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

A sequential sampling scheme for detecting infestation levels of tracheal mites (Heterostigmata: Tarsonemidae) in honey bee (Hymenoptera: Apidae) colonies.

The introduction of parasitic honey bee mites, the tracheal mite, Acarapis woodi (Rennie) in 1984 and the Varroa mite, Varroa jacobsoni, in 1987, has dramatically increased the winter mortality of honey bee, Apis mellifera L., colonies in many areas of the United States. Some beekeepers have minimized their losses by routinely treating their colonies with menthol, currently the only Environmental Protection Agency-approved and available chemical for tracheal mite control. Menthol is also expensive and can interfere with honey harvesting. Because of inadequate sampling techniques and a lack of information concerning treatment, this routine treatment strategy has increased the possibility that tracheal mites will develop resistance to menthol. It is important to establish economic thresholds and treat colonies with menthol only when treatment is warranted rather than treating all colonies regardless of infestation level. The use of sequential sampling may reduce the amount of time and effort expended in examining individual colonies and determining if treatment is necessary. Sequential sampling also allows statistically based estimates of the percentage of bees in standard Langstroth hives infested with mites while controlling for the possibility of incorrectly assessing the amount of infestation. On the average, sequential sampling plans require fewer observations (bees) to reach a decision for specified probabilities of type I and type II errors than are required for fixed sampling plans, especially when the proportion of infested bees is either very low or very high. We developed a sequential sampling decision plan to allow the user to choose specific economic injury levels and the probability of making type I and type II errors which can result inconsiderable savings in time, labor and expense.

Animals↗

Simultaneous X-Ray and TeV Observations of a Rapid Flare from Markarian 421.

Mrk 421 was observed for about 2 days with BeppoSAX in 1998 April as part of a worldwide multiwavelength campaign. A large, well-defined flare was observed in X-rays. The same flare was observed simultaneously at TeV energies by the Whipple Observatory gamma-ray telescope. These data provide (1) the first evidence that the X-ray and TeV intensities are well correlated on timescales of hours and (2) the first exactly simultaneous X-ray and TeV spectra. The results imply that the X-ray and TeV photons derive from the same region and from the same population of relativistic electrons. The physical parameters deduced from a homogeneous synchrotron self-Compton model for the spectral energy distribution yield electron cooling times close to the observed variability timescales.

Journal Article↗

Potent inhibition of influenza sialidase by a benzoic acid containing a 2-pyrrolidinone substituent.

On the basis of the lead compound 4-(N-acetylamino)-3-guanidinobenzoic acid (BANA 113), which inhibits influenza A sialidase with a Ki of 2.5 microM, several novel aromatic inhibitors of influenza sialidases were designed. In this study the N-acetyl group of BANA 113 was replaced with a 2-pyrrolidinone ring, which was designed in part to offer opportunities for introduction of spatially directed side chains that could potentially interact with the 4-, 5-, and/or 6-subsites of sialidase. While the parent structure 1-(4-carboxy-2-guanidinophenyl)pyrrolidin-2-one (8) was only a modest inhibitor of sialidase, the introduction of a hydroxymethyl or bis(hydroxymethyl) substituent at the C5' position of the 2-pyrrolidinone ring resulted in inhibitors (9 and 12, respectively) with low micromolar activity. Crystal structures of these inhibitors in complex with sialidase demonstrated that the substituents at the 5'-position of the 2-pyrrolidinone ring interact in the 4- and/or 5-subsites of the enzyme. Replacement of the guanidine in 12 with a hydrophobic 3-pentylamino group resulted in a large enhancement in binding to produce an inhibitor (14) with an IC50 of about 50 nM against influenza A sialidase, although the inhibition of influenza B sialidase was 2000-fold less. This represents the first reported example of a simple, achiral benzoic acid with potent (low nanomolar) activity as an inhibitor of influenza sialidase.

Benzoates↗

Hydrophobic benzoic acids as inhibitors of influenza neuraminidase.

Neuraminidase (NA) plays a critical role in the life cycle of influenza virus and is a target for new therapeutic agents. A new benzoic acid inhibitor (11) containing a lipophilic side chain at C-3 and a guanidine at C-5 was synthesized. The X-ray structure of 4-(N-acetylamino)-5-guanidino-3-(3-pentyloxy)benzoic acid in complex with NA revealed that the lipophilic side chain binds in a newly created hydrophobic pocket formed by the movement of Glu 278 to interact with Arg 226, whereas the guanidine of 11 interacts in a negatively charged pocket created by Asp 152, Glu 120 and Glu 229. Compound 11 was highly selective for type A (H2N2) influenza NA (IC50 1 microM) over type B (B/Lee/40) influenza NA (IC50 500 microM).

Antiviral Agents↗

Natural history and surgical outcomes for isolated discrete subaortic stenosis in children.

OBJECTIVE: To document the natural history and surgical outcomes for discrete subaortic stenosis in children. DESIGN: Retrospective review. SETTING: Tertiary care paediatric cardiology centres. PATIENTS: 92 children diagnosed between 1985 and 1998. MAIN OUTCOME MEASURES: Echocardiographic left ventricular outflow gradient (echograd), and aortic insufficiency (AI). RESULTS: The mean (SEM) age at diagnosis was 5.3 (0.4) years; the mean echograd was 30 (2) mm Hg, with AI in 22% (19/87) of patients. The echograd and incidence of AI increased to 35 (3) mm Hg and 53% (36/68) (p < 0.05) 3.6 (0.3) years later. The echograd at diagnosis predicted echograd progression and appearance of AI. 42 patients underwent surgery 2.2 (0.4) years after diagnosis. Preoperatively echograd and AI incidence increased to 58 (6) mm Hg and 76% (19/25) (p < 0.05). The echograd was 26 (4) mm Hg 3.7 (0.4) years postoperatively, with AI in 82% (31/38) of patients. Surgical morbidities included complete heart block, need for prosthetic valves, and iatrogenic ventricular septal defects. Eight patients underwent reoperation for recurrent subaortic stenosis. The age at diagnosis of 44 patients followed medically and 42 patients operated on did not differ (5.5 (0.6) v 5. 0 (0.6) years, p < 0.05). However, the echograd at diagnosis in the former was less (21 (2) v 40 (5) mm Hg, p < 0.05) and did not increase (23 (2) mm Hg) despite longer follow up (4.1 (0.4) v 2.2 (0. 4) years, p < 0.05). The incidence of AI at diagnosis and at last medical follow up was also less (14% (6/44) v 34% (13/38); 40% (17/43) v 76% (19/25), p < 0.05). CONCLUSIONS: Many children with mild subaortic stenosis exhibit little progression of obstruction or AI and need not undergo immediate surgery. Others with more severe subaortic stenosis may progress precipitously and will benefit from early resection despite risks of surgical morbidity and recurrence.

Aortic Valve Insufficiency↗

Testing the Uniform Needs Assessment Instrument for hospital discharge planning with older adults.

The Uniform Needs Assessment Instrument (UNAI) was developed to systematically assess the continuing care needs of high-risk older adults in response to the 1986 Omnibus Budget Reconciliation Act. Based on previous studies, a revised UNAI was tested with 103 hospitalized older adults, comparing usual discharge planning with the UNAI. High interrater reliability was obtained. The UNAI had high (> or = 85%) sensitivity and specificity when comparing needs identification on the UNAI with subjects' reported needs at 10 to 14 days after discharge. Overall, the UNAI was more effective (sensitive and specific).

Aftercare↗

Single lead VDD pacing in children with complete heart block.

OBJECTIVE: To evaluate clinically transvenous single lead VDD pacing in children with complete heart block. DESIGN: Case series. SETTING: Tertiary care unit of a pediatric teaching hospital. PATIENTS: Consecutive sample of children with complete heart block requiring pacing and meeting the criteria for VDD pacing. INTERVENTIONS: VDD single lead pacing systems (Thera VDD 8948 generator, Capsure VDD 5032 single pass lead) were implanted in nine children (mean age 10.7 years, 95% CI 8.9 to 12.3). All patients were reviewed six weeks and six months post-implantation with clinical review, detailed pacemaker interrogation, optimal device programming, treadmill exercise testing, 24 h Holter monitoring and echocardiography. RESULTS: Mean procedure time was 62.5 mins (CI 52 to 73), mean fluoroscopy time 3.8 mins (CI 2.4 to 5.1) and mean P wave sensing amplitude 2.75 mV (CI 2.5 to 3), without significant decrease during Valsalva manoeuvre (mean 2.4 mV, CI 2.2 to 2.8). Low pacing thresholds of mean amplitude 0.39 V (CI 0.38 to 0.4) were established at pulse width 0.5 ms. Two patients required early revision--one lead dislodged and one patient had a loose set screw. Follow-up showed satisfactory pacemaker function, and mean percentage atrioventricular (AV) synchronous pacing 96.8% (CI 93 to 99) at six weeks and 97% (CI 95 to 99) at six months. P wave sensing failures were less than 1%. AV synchronous pacing was maintained for more than 99% of the period of treadmill exercise testing. There was a significant mean increase in cardiac output of 24% (CI 8 to 40, P < 0.05) at rest in VDD mode compared with VVIR mode. CONCLUSIONS: Single lead VDD pacing is an effective and reliable method of 'physiological' rate responsive AV synchronous pacing in children with complete heart block and should be considered a viable alternative to dual lead pacing systems.

Adolescent↗

Single-tooth implant-supported restorations in the anterior maxilla.

With the development of advanced surgical techniques, implants can now be utilized in a variety of applications, including replacement of a single tooth. The form of an artificial restoration is determined by the existing tooth morphology and periodontal architecture; when placing single-tooth implants, the original structure of the tooth and periodontium must be recreated. Osseointegrated single-tooth implants have a success rate that is comparable to that of implant-supported prostheses in totally edentulous patients; a 98.5% success rate has been reported following 3 years in situ. The learning objective of this article is to gain an understanding of pretreatment guidelines, such as soft tissue considerations, bone dimension, root morphology, and site preparation with osteotomes for single-tooth implant placement. The review also includes the discussion of the placement of single-tooth implants, flap design, prosthetic considerations, and the final restoration. Two case reports are presented to document and illustrate the clinical procedure.

Adult↗

NMR applications in complex food systems.

The rheological and functional properties of food components are related to their molecular structure, morphology, and atomic mobilities. NMR provides a powerful tool for elucidating chemical structures, molecular conformations, and interactions of components in food systems. Quantitative analysis of sugars, fats, and other principal compounds in complex food systems was achieved by high-resolution liquid NMR. In addition to information available from liquid experiments, solids NMR experiments can reveal differences and changes in crystal packing of structures in food model systems. Interpretation of experimental results is enhanced by molecular modeling of key food compounds. Models for fat crystallization are carried out to enhance understanding of the molecular structures involved in the fat crystallization process. Recently, MRI has also shown significant impact on food science and technology. Some examples of NMR applications are given in this presentation.

Crystallization↗

Prenatal diagnosis of cerebellar hemorrhage: medicolegal implications.

Perinatal brain damage and compromised long-term neurologic outcome have been a topic of major concern and continuing debate. Until recently the occurrence of fetal brain injury was attributed to intrapartum events. However, evidence continues to accumulate that neurologic damage can occur during fetal life unrelated to intrapartum events. We report a case of massive cerebellar hemorrhage of unknown cause diagnosed by ultrasonography at 36 weeks of gestation after decreased fetal movements. Fetal heart rate pattern and Doppler flow study of cerebral arteries are correlated with neuropathologic findings, and the medicolegal aspects of this condition are discussed.

Adult↗

Human antibodies reactive with beta-amyloid protein in Alzheimer's disease.

Four human B cell lines established by Epstein-Barr viral transformation of B cells from a patient with a clinical diagnosis of Alzheimer's disease (AD) were found to secrete antibodies that react with plaques and cerebrovascular blood vessels in AD brain in a staining profile characteristic of beta-amyloid protein (beta-AP) in AD brain. Two of these antibodies were shown to be reactive with a rare plaque in a normal brain. In these studies, immunofluorescence and avidin-biotin complex immunoperoxidase methodology were used to determine antibody reaction, and thioflavine S was used to double label amyloid and neurofibrillary tangles. The four antibodies also reacted with neurons in normal and AD brain. Absorption studies, dot immunoblots, and enzyme-linked immunosorbent assays with beta-amyloid peptides 1-28 (beta-A1-28) and 1-40 (beta-A1-40) indicate the major determinant of the reactive epitope is located in the region of amino acids 1-28 of beta-AP. However, inhibition studies demonstrate a significant contribution to the antigenic determinant by the 29-40 region of the beta-A1-40. These antibodies represent the first human autoantibodies against beta-AP. The pathological significance of these autoantibodies is discussed.

Aged↗

Placental chorioangioma: prenatal diagnosis and clinical significance.

We report the prenatal diagnosis of placental chorioangioma in a 32-week intrauterine pregnancy associated with polyhydramnios and enlarged fetal cardiac size that resulted in intrauterine fetal death. Ultrasound appearance, pathophysiology, and clinical significance of this entity are discussed.

Adolescent↗

Surgically created Wolff-Parkinson-White syndrome after Fontan operation.

The Wolff-Parkinson-White syndrome is caused by a congenital accessory connection between the atrium and ventricle. We describe a case of symptomatic Wolff-Parkinson-White syndrome that arose after a Björk modification of the Fontan operation. Invasive electrophysiologic and intraoperative mapping indicated that the surgically created atrioventricular connection was functioning as an accessory pathway. Surgical dissection and cryoablation abolished the symptoms and the preexcitation.

Adolescent↗

Posttranslational modifications of rat proenkephalin overexpressed in Chinese hamster ovary cells.

Rat proenkephalin was overexpressed in Chinese hamster ovary cells using the dihydrofolate reductase-coupled genetic amplification method. About 2 mg purified protein could be obtained from 250 ml conditioned medium; multiple successive harvests could be obtained from the same roller bottle. Degradation of proenkephalin released into the conditioned medium was reduced significantly in the presence of 2% fetal bovine serum. Forty-eight percent of recombinant proenkephalin was glycosylated; glycosylation could be entirely prevented by the addition of tunicamycin. Two-dimensional isoelectric focusing experiments showed that recombinant proenkephalin exhibited considerable charge heterogeneity, with two major unglycosylated isoelectric forms and six or seven glycosylated isoelectric forms. The estimated isoelectric points of the major unglycosylated proenkephalins were 6.0 and 6.1, while glycosylated proenkephalins ranged in pI from 5.7-6.1. Some of this isoelectric heterogeneity is due to phosphorylation; [32P] orthophosphate was readily incorporated into serine residues within newly synthesized proenkephalin.

Animals↗